Interleukin-4 Drives Tumor-Associated Macrophage Polarization to Promote Tumor Gr

Interleukin-4驱动肿瘤相关巨噬细胞极化促进肿瘤生长

• 批准号: 8592689
• 负责人: Steven Allen
• 金额: $ 3.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-14 至 2017-01-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592689
• 关键词: Area; Automobile Driving; Breast; Cause of Death; Cell Line; Cell Nucleus; Characteristics; Coupled; Diagnosis; Environment; Fostering; Future; Goals; Growth; Immune response; Immunity; Inflammation; Inflammatory; Interleukin 4 Receptor; Interleukin-4; Knockout Mice; Knowledge; Lead; Life; Malignant Neoplasms; Mediating; Methods; Mission; Modeling; Mus; NF-kappa B; Neoplasm Metastasis; Neoplasms in Vascular Tissue; Nuclear; Nuclear Translocation; Pathway interactions; Patients; Phenotype; Play; Primary Neoplasm; Public Health; Research; Research Personnel; Role; STAT6 Transcription Factor; Scientist; Signal Transduction; Source; Stimulus; T-Lymphocyte; TNFRSF5 gene; Tissues; Tumor Cell Invasion; Tumor Cell Line; United States; United States National Institutes of Health; allergic response; angiogenesis; burden of illness; cancer therapy; cell type; cytokine; in vivo; macrophage; malignant breast neoplasm; microbicide; migration; outcome forecast; overexpression; p65; prevent; public health relevance; response; tumor; tumor growth; tumor microenvironment; tumor progression

DESCRIPTION (provided by applicant): Despite many advances in the battle against cancer, it remains a dreaded diagnosis and a leading cause of death in the United States. The rationale and hope for this proposed research is that any and all knowledge gained in understating how cancer progresses and infiltrates areas of the body brings, not only scientists, but the patients and public closer to achieving their common goal of complete eradication of cancers. The environment surrounding tumors is known to be one of smoldering inflammation and one cell type, known as a tumor-associated macrophage (TAM), prevalent in this environment has been shown to promote many aspects of cancer. TAMs foster tumor progression in multiple ways; they support new tumor blood vessel growth, tumor cell invasion, and even enhance metastasis. A key objective of this proposal is to understand the origin of the cellular signals that stimulate TAM's pro-tumor functions and how these signals act on TAMs. The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus, this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life. The methods employed in order to achieve this goal will be to study tumor models in mice. Tumors will be generated that either do or do not secrete a certain signal, interleukin-4 (IL-4), and then these tumors investigated in mice that either do or do not have the ability to produce IL-4. Also, IL-4 and its effects on TAMs both with and without the IL-4 receptor will be studied to help discern how it might play a role in promoting cancer. The specific aims of this project are to determine the effects of IL-4 secreted from the tumor on tumor growth, metastasis, and TAMs and to understand how IL-4 signals to TAMs to achieve its pro- cancer consequences. It is expected that the impact of the results of this study will be in allowing researchers to target TAMs with future anti-cancer therapy from multiple avenues.

描述（由申请人提供）：尽管在与癌症的斗争中取得了许多进步，但它仍然是一种可怕的诊断，也是美国人死亡的主要原因。这项拟议研究的基本原理和希望是，在理解癌症如何进展和浸润身体部位方面获得的任何和所有知识，不仅使科学家，而且使患者和公众更接近于实现彻底根除癌症的共同目标。已知肿瘤周围的环境是一种闷烧炎症和一种被称为肿瘤相关巨噬细胞（TAM）的细胞类型，在这种环境中普遍存在，已被证明可促进癌症的许多方面。tam通过多种方式促进肿瘤进展；它们支持新的肿瘤血管生长，肿瘤细胞侵袭，甚至促进肿瘤转移。这一建议的一个关键目标是了解刺激的细胞信号的起源